Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1522282 (EMT)
2,868 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Numerous studies suggest that several long non-coding RNAs (lncRNAs) play critical roles in bladder cancer development and progression. Long non-coding RNA urothelial cancer-associated 1 (lncRNA-UCA1) is highly expressed in bladder cancer tissues and cells, and it has been shown to play an important role in regulating aggressive phenotypes of bladder cancer cells. However, little is known about the molecular mechanism of lncRNA-UCA1-mediated bladder cancer cell migration and invasion. Here, we show that overexpression of lncRNA-UCA1 could induce EMT and increase the migratory and invasive abilities of bladder cancer cells. Mechanistically, lncRNA-UCA1 induced EMT of bladder cancer cells by upregulating the expression levels of zinc finger E-box binding homeobox 1 and 2 (ZEB1 and ZEB2), and regulated bladder cancer cell migration and invasion by tumor suppressive hsa-miR-145 and its target gene the actin-binding protein fascin homologue 1 (FSCN1). Furthermore, we also observed a positive correlation between lncRNA-UCA1 and ZEB1/2 expression, and a negative correlation between lncRNA-UCA1 and hsa-miR-145 expression in bladder cancer specimens. Importantly, we found that lncRNA-UCA1 repressed hsa-miR-145 expression to upregulate ZEB1/2, whereas the suppression of hsa-miR-145 could upregulate lncRNA-UCA1 expression in bladder cancer cells. Moreover, the binding site for hsa-miR-145 within exons 2 and 3 of lncRNA-UCA1 contributed to the reciprocal negative regulation of lncRNA-UCA1 and hsa-miR-145. Taken together, our results identified that lncRNA-UCA1 enhances bladder cancer cell migration and invasion in part through the hsa-miR-145/ZEB1/2/FSCN1 pathway. Therefore, lncRNA-UCA1 might act as a promising therapeutic target for the invasion and metastasis of bladder cancer.
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PMID:Long non-coding RNA urothelial cancer-associated 1 promotes bladder cancer cell migration and invasion by way of the hsa-miR-145-ZEB1/2-FSCN1 pathway. 2654 36

Oral squamous cell carcinoma (OSCC) prognosis is related to clinical stage and histological grade. However, this stratification needs to be refined. We conducted a comparative proteome study in microdissected samples from normal oral mucosa and OSCC to identify biomarkers for malignancy. Fascin and plectin were identified as differently expressed and both are implicated in several malignancies, but the clinical impacts of aberrant fascin and plectin expression in OSCCs remains largely unknown. Immunohistochemistry and real-time quantitative PCR were carried out in ex vivo OSCC samples and cell lines. A loss-of-function strategy using shRNA targeting fascin was employed to investigate in vitro and in vivo the fascin role on oral tumorigenesis. Transfections of microRNA mimics were performed to determine whether the fascin overexpression is regulated by miR-138 and miR-145. We found that fascin and plectin are frequently upregulated in OSCC samples and cell lines, but only fascin overexpression is an independent unfavorable prognostic indicator of disease-specific survival. In combination with advanced T stage, high fascin level is also an independent factor of disease-free survival. Knockdown of fascin in OSCC cells promoted cell adhesion and inhibited migration, invasion and EMT, and forced expression of miR-138 in OSCC cells significantly decreased the expression of fascin. In addition, fascin downregulation leads to reduced filopodia formation and decrease on paxillin expression. The subcutaneous xenograft model showed that tumors formed in the presence of low levels of fascin were significantly smaller compared to those formed with high fascin levels. Collectively, our findings suggest that fascin expression correlates with disease progression and may serve as a prognostic marker and therapeutic target for patients with OSCC.
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PMID:Fascin promotes migration and invasion and is a prognostic marker for oral squamous cell carcinoma. 2908 20